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Ly49H signaling through DAP10 is essential for optimal natural killer cell responses to mouse cytomegalovirus infection

The activating natural killer (NK) cell receptor Ly49H recognizes the mouse cytomegalovirus (MCMV) m157 glycoprotein expressed on the surface of infected cells and is required for protection against MCMV. Although Ly49H has previously been shown to signal via DAP12, we now show that Ly49H must also...

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Autores principales: Orr, Mark T., Sun, Joseph C., Hesslein, David G.T., Arase, Hisashi, Phillips, Joseph H., Takai, Toshiyuki, Lanier, Lewis L.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715124/
https://www.ncbi.nlm.nih.gov/pubmed/19332875
http://dx.doi.org/10.1084/jem.20090168
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author Orr, Mark T.
Sun, Joseph C.
Hesslein, David G.T.
Arase, Hisashi
Phillips, Joseph H.
Takai, Toshiyuki
Lanier, Lewis L.
author_facet Orr, Mark T.
Sun, Joseph C.
Hesslein, David G.T.
Arase, Hisashi
Phillips, Joseph H.
Takai, Toshiyuki
Lanier, Lewis L.
author_sort Orr, Mark T.
collection PubMed
description The activating natural killer (NK) cell receptor Ly49H recognizes the mouse cytomegalovirus (MCMV) m157 glycoprotein expressed on the surface of infected cells and is required for protection against MCMV. Although Ly49H has previously been shown to signal via DAP12, we now show that Ly49H must also associate with and signal via DAP10 for optimal function. In the absence of DAP12, DAP10 enables Ly49H-mediated killing of m157-bearing target cells, proliferation in response to MCMV infection, and partial protection against MCMV. DAP10-deficient Ly49H(+) NK cells, expressing only Ly49H–DAP12 receptor complexes, are partially impaired in their ability to proliferate during MCMV infection, display diminished ERK1/2 activation, produce less IFN-γ upon Ly49H engagement, and demonstrate reduced control of MCMV infection. Deletion of both DAP10 and DAP12 completely abrogates Ly49H surface expression and control of MCMV infection. Thus, optimal NK cell–mediated immunity to MCMV depends on Ly49H signaling through both DAP10 and DAP12.
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spelling pubmed-27151242009-10-13 Ly49H signaling through DAP10 is essential for optimal natural killer cell responses to mouse cytomegalovirus infection Orr, Mark T. Sun, Joseph C. Hesslein, David G.T. Arase, Hisashi Phillips, Joseph H. Takai, Toshiyuki Lanier, Lewis L. J Exp Med Article The activating natural killer (NK) cell receptor Ly49H recognizes the mouse cytomegalovirus (MCMV) m157 glycoprotein expressed on the surface of infected cells and is required for protection against MCMV. Although Ly49H has previously been shown to signal via DAP12, we now show that Ly49H must also associate with and signal via DAP10 for optimal function. In the absence of DAP12, DAP10 enables Ly49H-mediated killing of m157-bearing target cells, proliferation in response to MCMV infection, and partial protection against MCMV. DAP10-deficient Ly49H(+) NK cells, expressing only Ly49H–DAP12 receptor complexes, are partially impaired in their ability to proliferate during MCMV infection, display diminished ERK1/2 activation, produce less IFN-γ upon Ly49H engagement, and demonstrate reduced control of MCMV infection. Deletion of both DAP10 and DAP12 completely abrogates Ly49H surface expression and control of MCMV infection. Thus, optimal NK cell–mediated immunity to MCMV depends on Ly49H signaling through both DAP10 and DAP12. The Rockefeller University Press 2009-04-13 /pmc/articles/PMC2715124/ /pubmed/19332875 http://dx.doi.org/10.1084/jem.20090168 Text en © 2009 Orr et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Orr, Mark T.
Sun, Joseph C.
Hesslein, David G.T.
Arase, Hisashi
Phillips, Joseph H.
Takai, Toshiyuki
Lanier, Lewis L.
Ly49H signaling through DAP10 is essential for optimal natural killer cell responses to mouse cytomegalovirus infection
title Ly49H signaling through DAP10 is essential for optimal natural killer cell responses to mouse cytomegalovirus infection
title_full Ly49H signaling through DAP10 is essential for optimal natural killer cell responses to mouse cytomegalovirus infection
title_fullStr Ly49H signaling through DAP10 is essential for optimal natural killer cell responses to mouse cytomegalovirus infection
title_full_unstemmed Ly49H signaling through DAP10 is essential for optimal natural killer cell responses to mouse cytomegalovirus infection
title_short Ly49H signaling through DAP10 is essential for optimal natural killer cell responses to mouse cytomegalovirus infection
title_sort ly49h signaling through dap10 is essential for optimal natural killer cell responses to mouse cytomegalovirus infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715124/
https://www.ncbi.nlm.nih.gov/pubmed/19332875
http://dx.doi.org/10.1084/jem.20090168
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